Aim – the paper presents one or well documented theories of the origin of dementia in Alzheimer's disease, concerning amyloid-beta precursor protein cleavage.
Review – There at least two pathways of this protein proteolytic degradation, i.e. either amyloidogenic, generating amyloid beta, or non-amyloidogenic, generating soluble proteins. Amyloid beta, which is a major component of senile plaques in the brain of patients with Alzheimer's disease, is generated via the amyloidogenic pathway from amyloid-beta precursor protein through its sequential proteolityc cleavage catalyzed by beta- and gamma-secretases. Beta-secretase and gamma-secretase were identified as membrane-tethered aspartyl proteases. The presenilins are required for the proteolytic cleavage catalyzed by gamma-secretase. Mutations in the genes encoding for presenilins and amyloid-beta precursor protein are the cause of early-onset familial Alzheimer's disease. For these reasons secretases are considered an important therapeutic target in Alzheimer's disease.
Conclusion – The proteolytic cascade hypothesis is well documented, but it may relate only to a small part or pathways leading to the pathology of brain injury with subsequent dementia in Alzheimer's disease.